Atherosclerosis is a progressive disease wherein fatty, fibrous, calcific, or thrombotic deposits produce atheromatous plaques, within and beneath the intima which is the innermost layer of arteries. Atherosclerosis tends to involve large and medium sized arteries. The most commonly affected are the aorta, iliac, femoral, coronary, and cerebral arteries. Clinical symptoms occur because the mass of the atherosclerotic plaque reduces blood flow through the afflicted artery, thereby compromising tissue or organ function distal to it.
The mortality and morbidity from ischemic heart disease results primarily from atheromatous narrowings of the coronary arteries. Although various medical and surgical therapies may improve the quality of life for most patients with coronary atherosclerosis, such therapies do not favorably change the underlying anatomy responsible for the coronary luminal narrowings. Until recently, there has not been a non-surgical means for improving the perfusion of blood through the lumina of coronary arteries compromised by atheromatous plaque.
Percutaneous transluminal coronary angioplasty has been developed as an alternative, non-surgical method for treatment of coronary atherosclerosis. During cardiac catheterization, an inflatable balloon is inserted in a coronary artery in the region of coronary narrowing. Inflation of the balloon for 15-30 seconds results in an expansion of the narrowed lumen or passageway. Because residual narrowing is usually present after the first balloon inflation, multiple or prolonged inflations are routinely performed to reduce the severity of the residual stenosis or tube narrowing. Despite multiple or prolonged inflations, a mild to moderately severe stenosis usually is present, even after the procedure is otherwise performed successfully.
The physician will often prefer not to dilate lesions that are not severe because there is a good chance that they will recur. Because the occlusion recurs frequently, conventional angioplasty is often considered to be a suboptimal procedure. As a result, it is sometimes attempted only when a patient does not wish to undergo major cardiac surgery.
There are several reasons why the lesions reappear. One is that small clots form on the arterial wall. Tears in the wall expose blood to foreign material and proteins, such as collagen, which are highly thrombogenic. Resulting clots can grow gradually, or can contain growth hormones which are released by platelets within the clot. Additionally, growth hormones released by other cells, such as macrophages, can cause smooth muscle cells and fibroblasts in the region to multiply. Further, there is often a complete loss of the normal single layer of cells constituting the endothelial lining following angioplasty. This layer normally covers the internal surface of all vessels, rendering that surface compatible, i.e. non-thrombogenic and non-reactive with blood. Mechanically, when an angioplasty balloon is inflated, the endothelial cells are torn away. Combination of the loss of the endothelial layer and tearing within the wall often generates a surface which is quite thrombogenic.
Prior art angioplasty procedures also produce injuries in the arterial wall which become associated with inflammation. White cells will migrate to the area and will lay down scar tissue. Any kind of inflammatory response may cause the growth of new tissue. Restenosis or recurrence of the obstruction results because the smooth muscle cells which normally reside within the arterial wall proliferate. Such cells migrate to the area of the injury and multiply in response thereto.
It therefore appears that in order to combat problems associated with cumulating plaque, attention must be paid to: (1) the importance of thrombus; (2) inflammatory changes; and (3) proliferation. Any combination of these factors probably accounts for most cases of restenosis.
In order to address such problems, the cardiology community needs to administer drugs which are biocompatible and not induce toxic reactions. Therefore, it would be helpful to invoke a technique which allows localized administration of drugs that counteract clotting, interfere with inflammatory responses, and block proliferative responses. However, many such drugs when administered are toxic and are associated with potentially serious side effects which make the treatment and prevention of restenosis impractical. Accordingly, even though there is a number of potentially useful drugs, there is a tendency to avoid using them.
One of the other major problems with conventional methods of treatment is that the injured arterial wall exhibits a reduced hemocompatability compared to that associated with a normal arterial wall. Adverse responses which are associated with reduced hemocompatability include platelet adhesion, aggregation, and activation; potential initiation of the coagulation cascade and thrombosis; inflammatory cell reactions, such as adhesion and activation of monocytes or macrophages; and the infiltration of leukocytes into the arterial wall. Additionally, cellular proliferation results in the release of a variety of growth factors. Restenosis probably results from one or a combination of such responses.
Methods for treating atherosclerosis are disclosed in my U.S. Pat. No. 4,512,762 which issued on Apr. 23, 1985, and which is herein incorporated by reference. This patent discloses a method of injecting a hematoporphyrin into a mammal for selective uptake into the atheromatous plaque, and delivering light to the diseased vessel so that the light activates the hematoporphyrin for lysis of the plaque. However, one of the major problems with such treatments is that the thermal energy does not produce a significant rise in temperature. Also, a flap of material occasionally is formed during the treatment which, after withdrawal of the instrumentation, falls back into the artery, thereby causing abrupt reclosure. This may necessitate emergency coronary artery bypass surgery. Accordingly, such techniques often provide only a temporary treatment for symptoms associated with arterial atherosclerosis.
My U.S. Pat. No. 4,799,479 was issued on Jan. 24, 1989 and is also herein incorporated by reference. This patent discloses a method used in percutaneous transluminal coronary angioplasty wherein a balloon is heated upon inflation. Disrupted tissues of plaque in the arterial wall are heated in order to fuse together fragmented segments of tissue and to coagulate blood trapped with dissected planes of tissues and within fissures created by the fracture. Upon subsequent balloon deflation, a smooth cylindrically shaped channel results. Such heating in that disclosure, however, is used to bond tissue to tissue--not to bond a bioprotective material to tissue.
Approaches such as those disclosed in U.S. Pat. Nos. 4,512,762 and 4,799,479, however, are directed mainly to producing an enhanced luminal result wherein a smooth luminal wall is produced. Problems of biocompatability, including thrombosis, and proliferation of cells tend to remain. Accordingly, the need has arisen to enable a physician to treat patients having atherosclerosis so that the problems of reduced hemocompatability and restenosis are avoided.
As a result of problems remaining unsolved by prior art approaches, there has been a growing disappointment in the cardiology community that until now, no new technology or procedure has been available to dramatically reduce the rate of restenosis.